The long term goal of this prosal is to study the significance and mechanism of the interaction of the Abl tyrosine kinase with Pag, for which we created a knock-out mouse. Abl is a non-receptor tyrosine kinase which has been studied now for over the past two decades, and yet its function is still not understood. Its involvement in cell cycle, cell growth and apoptosis links Abl to oncogenetic pathways. Pag, a protein with antioxidant actvity is activated by free radicals, and is inhibiting the kinase activity of Abl. One part of the study will focus on determination of the interactionsites of Abl and Pag, and the regulation of this interaction by free radicals. Additionally, we will focus on the physiological role of Pag. These studies will be done in murine embryo fibroblasts (MEFs) isolated from Pag -/-mice and in the Pag -/- mice.